Cadherin activity is required for activity-induced spine remodeling

Neural activity induces the remodeling of pre- and postsynaptic membranes, which maintain their apposition through cell adhesion molecules. Among them, N-cadherin is redistributed, undergoes activity-dependent conformational changes, and is required for synaptic plasticity. Here, we show that depolarization induces the enlargement of the width of spine head, and that cadherin activity is essential for this synaptic rearrangement. Dendritic spines visualized with green fluorescent protein in hippocampal neurons showed an expansion by the activation of AMPA receptor, so that the synaptic apposition zone may be expanded. N-cadherin-venus fusion protein laterally dispersed along the expanding spine head. Overexpression of dominant-negative forms of N-cadherin resulted in the abrogation of the spine expansion. Inhibition of actin polymerization with cytochalasin D abolished the spine expansion. Together, our data suggest that cadherin-based adhesion machinery coupled with the actin-cytoskeleton is critical for the remodeling of synaptic apposition zone

急性期脳梗塞患者における血液透析は短期あるいは長期死亡の危険因子である

慢性腎臓病は脳血管障害を含む心血管疾患の独立した危険因子である．透析患者の脳卒中発症リスクは非透析患者に比較して高い事が報告されている．しかし，血液透析施行と，急性期脳梗塞患者の短期及び長期死亡の関連は不明である．今回我々は，急性期脳梗塞患者における院内死亡及び退院１年後の死亡に透析が関与するかどうか検討した．2007年４月～2015年３月に当科に入院した発症24時間以内の脳梗塞患者を後ろ向きに検討した．血液透析の有無により，血液透析あり群となし群に分類し，臨床背景を比較した．加えて末期腎不全患者（eGFR15ml 分/1.73m2以下）において，血液透析あり群となし群に分類し，臨床背景を比較した．更に院内及び退院後１年以内の死亡の有無により生存群と死亡群に分けて，血液透析を含む関連因子を多変量解析で検討した．急性期脳梗塞1,894例が登録された．平均年齢は73.8±11歳，男性は1,122人（59.2%）であった．65例（3.4%）が維持透析中であった．透析群と非透析群の背景因子の比較について示す．年齢（69.6±11.9 vs. 73.7±12歳　P ＝0.013）は透析群が有意に若く，高血圧の既往（91% vs. 70% P<0.001），糖尿病の既往（45% vs. 24% P<0.001），脳底動脈の閉塞（7% vs. 2% P=0.001）が透析群では有意に高かった．また全体の院内死亡率は5.3%（96/1,894人）であった．透析群は非透析群と比較して院内死亡率（14% vs. 5% P=0.001）は有意に高かった．末期腎不全患者間でも，透析群は非透析群と比較して院内死亡率（15% vs. 0% P=0.038）は有意に高かった．院内死亡群と生存群に分けて多変量解析をしたところ入院時の年齢（オッズ比（OR）1.1，95%CI1.02-1.23，P=0.013），入院時NIHSS 高値（OR1.2，95%CI1.12-1.38，P=0.012），脳底動脈の閉塞（OR3.3，95%CI1.32-3.84，P=0.011），透析群（OR7.8，95%CI2.259-26.79，P=0.001）が独立した関連因子であった．次に退院後１年以内の死亡率は7.9%（226/1,798人）であった．透析群は非透析群と比較して１年後死亡率（21% vs. 12%, P=0.001）は有意に高かった．末期腎不全患者間でも，透析群は非透析群と比較して院内死亡率（22% vs. 8%，P=0.042）は有意に高かった．１年以内の死亡率と生存群に分けて多変量解析を実施したところ年齢（OR1.1，95%CI1.07-1.28， P=0.014），内頚動脈の閉塞（OR1.9，95%CI1.34-4.62， P=0.009），退院時mRS3-5（OR2.3，95%CI1.6-3.2，P=0.008），透析群（OR2.5，95%CI1.34-4.62，P=0.001）が独立した危険因子であった．以上より血液透析は脳梗塞後の短期及び長期死亡の因子である．The chronic kidney disease is an independent risk factor of the cardiovascular diseases including stroke. Hemodialysis (HD) is reported to be a risk factor for cerebrovascular events. However, it is unclear whether HD is a risk factor for short or long term mortality in ischemic stroke patients. The aim of the present study was to investigate the whether a short or long term mortality of stroke patients receiving HD is higher than that of those without HD. From April 2007 to May 2015, we retrospectively enrolled ischemic stroke patients within 24h of stroke onset who were admitted to our hospital. We divided the patients into two groups according to presence and absence of receiving HD (HD group and non-HD group). Additionally, we divided the patients with end stage renal failure (<eGFR15ml/min/1.73m2) into HD group and non-HD group. We compared the clinical characteristics and the mortality rate at discharge and 1year after stroke onset between the two groups. The factors associated with death were investigated by multivariate logistic regression analysis. 1894 patients (1,122 males; (59.2%), mean age 73.8 ± 12 years) were enrolled. 65 patients (3.4%) had HD. HD group was younger (69.6 ± 11.9 vs. 73.7 ± 12.0 year, P = 0.013), and hypertension (91 % vs. 70 %, P < 0.001) diabetes mellitus (45% vs. 24%, P < 0.001) and basilar artery occlusion (7 % vs. 2%, P = 0.001) were more frequently observed than in the non-HD group. In-hospital mortality was 5.3% (96/1,894 patients). HD group had a high mortality rate compared with non HD group (14%vs. 5%, P=0.001). In end stage renal failure, HD group had a high mortality rate compared with the non HD group (15% vs. 0%, P = 0.038). Multivariate logistic regression analysis demonstrated that age per 1year increase (OR 1.1, 95%CI 1.02-1.23, P = 0.013), higher NIHSS score on admission, (OR 1.2, 95% CI 1.12-1.38, P = 0.012), basilar artery occlusion (OR 3.3, 95% CI 1.32-3.84, P = 0.011), and HD (OR 4.1, 95%CI 1.73-9.97, P = 0.001) were independent factors associated with in-hospital death. Next, after hospital discharge, 7.9% of patients died within 1 year. HD group had a high mortality rate compared with the non HD group (21% vs. 12%, P = 0.001). In end stage renal failure, HD group had a high mortality rate compared with the non HD group (22% vs. 8%, P = 0.042). On multivariate regression analysis, age per 1year increase (OR 1.1, 95%CI 1.07-1.28, P = 0.014), poor functional outcome (modified Ranking Scale (3-5)) at discharge (OR 2.3, 95%CI 1.64-3.23, P = 0.008), Internal carotid artery occlusion (OR 1.9, 95% CI 1.23-3.34, P = 0.009) and HD (OR 2.5, 95%CI 1.34-4.62, P = 0.001) were independent factors associated with death within 1year of stroke onset. Therefore, HD was independently associated with short or long term mortality

Correlation between length of stay in acute stroke wards and the functional prognosis after comprehensive rehabilitation

　脳卒中発症後の機能予後改善には回復期リハビリテーションが有効である．急性期病棟から回復期リハビリテーション病棟に早期に移ることが，機能予後改善につながる可能性がある．本研究では，急性期病棟の在院期間と長期予後改善効果の関連性を検討することを目的とした．2018年１月1日から2018年12月31日までに川崎医科大学附属病院脳卒中科に入院した急性期脳卒中症例のうち，回復期リハビリテーション病棟に転棟・転院した症例を対象とした．脳卒中科退院時に比し，一年後に modified Rankin scale が１以上改善した症例を改善有と定義した．改善有と関連する患者背景因子，入院中の診療データについて検討を行った．関連性はカイ二乗検定を用いて評価し，有意な関連性を示した因子についてはロジスティック回帰分析を用いて解析した．対象期間に入院した急性期脳卒中408例中，回復期リハビリテーション病棟に転棟・転院したのは142例であった（男性90人，中央値76.0歳）．改善有は57例であり，在院期間の第一四分位である17日未満で回復期病棟に移った群で改善有が有意に多かった（P < 0.01）．ロジスティック回帰分析でも急性期病棟の在院期間が短い（17日未満）ことが改善有と独立して関連した．急性期脳卒中患者の急性期病棟在院期間を短縮することが機能予後改善につながることが示唆された．　Neurological symptoms and functional disability of stroke survivors can be improved through comprehensive rehabilitation in the post-acute phase. Early transfer from the stroke unit to the rehabilitation ward possibly leads to an improvement of functional prognosis. The purpose of this study was to investigate the relationship between the length of stay in the stroke unit and the long-term prognosis improvement. The study involved acute stroke patients admitted to the Department of Stroke, Kawasaki Medical School Hospital between January 1, 2018 and December 31, 2018. Specifically, those selected and included in the study were patients eventually transferred to a rehabilitation department or hospital. Improvement of functional prognosis was defined as a 1-point decrease on the modified Rankin scale at 1 year compared with that at the time of discharge from the stroke department. Factors associated with the improvement group were evaluated using the chi-square test and then logistic regression analysis. Of the 408 patients with acute stroke admitted during the study period, 142 were transferred to rehabilitation centers (90 men, median age: 76.0 years). Fifty-seven patients had improvement. The rate of improvement was significantly higher in the group transferred to the rehabilitation ward by day 17, the first quartile of time in the stroke unit (p < 0.01). Logistic regression analysis also showed that a shorter length of stay (< 17 days) in the stroke unit was independently associated with improvement. The results suggest that early initiation of comprehensive rehabilitation in the post-acute phase leads to improved functional outcomes of patients with acute stroke